The objectives of this research are to evaluate the importance of tissue and vascular smooth muscle hypoxia in determining cardiovascular responses to hemorrhage, and to increase our understanding of the local regulation of blood flow during circulatory stress (with and without therapeutic drugs). The microcirculation of the mesentery, cremaster muscle, and cheek pouch will be observed by in vivo microscopy in anesthetized hamster and rats subjected to prolonged hemorrhage. Microvessel diameters will be measured to assess changes in vascular resistance and capacitance during the compensatory and decompensatory stages of the stress. Intercapillary distance will also be measured as an indication of exchange vessel function and blood flow distribution within the tissues. During the hypovolemic periods and following reinfusion of shed blood volume, P02 will be measured with microelectrodes in the tissue and on microvessel surfaces. These measurements will serve as indices of oxygen availability to parenchymal cells and vascular smooth muscle, respectively. Oxygen availability to the microcirculation will be controlled by suffusing the tissues with high and low P02 saline solution. This research should contribute to our understanding of the cause of irreversibility in shock and aid in the development of effective therapeutic approaches to low flow states.